ESPE Abstracts (2017) 89 FC3.1

Neonatal Diabetes Owned to Potassium Channel Mutation: Response to Sulfonylureas According to the Genotype

Laure Garcina, Anne-Laure Fauretb, Helene Cavéb, Michel Polaka & Jacques Beltranda


aService D’endocrinologie Et Diabétologie Pédiatrique, Hôpital Universitaire Necker Enfants Malades, AP-HP, Paris, France; bDepartement De Génétique, Hôpital Robert Debré, AP-HP, Paris, France


Introduction / aim: Neonatal diabetes owned to potassium channel mutation can be successfully treated by sulfonylureas (SU). No study has reported SU efficiency according to the genotype.

Method: Review of literature conducted in accordance with the control criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Search engine used: PubMed and the Cochrane Library database. Selection of clinical report, case reviews and meta-analyzes published in English, German or French before May 2017. Data collected: patient characteristics and SU treatment, success rate and presumed failure of SU treatment, characteristics of genetic mutations, HbA1c before and after switch, adverse effects. 84/150 studies selected.

Results: 393/449 patients were successfully treated by SU (87.5%). The median age at diagnosis was 60 days of age (0 to 20 years of age), and at sulfonylureas initiation was 48 months of age (0 to 63 years). In 32 patients, SU were introduced only in adulthood. The median dose of SU required to maintain a good glycemic control was 0.47 mg/kg per day (0 to 2.8 mg/kg per day). The median dose in patients with ABCC8 mutations was 0.4 mg/kg per day (0.03–1.8 mg/kg per day) versus 0.49 mg/kg per day (0.017–2)., 6) for mutations of KCNJ1. The median HbA1c of the patients was 8.2% before SU treatment versus 6.2% after the start of treatment. Six mutations of the KCNJ11 gene (C166Y, G334D, G334V, I296L, L164P, Q52L) on the 43 reported and four mutations of the ABCC8 gene ((F132V, N72S, R1182W, R825W) on the 39 reported have never been successfully treated. five mutations of KCNJ11 and 5 mutations of ABCC8 required high doses of SU (>0.79 mg/kg per day) to allow insulin discontinuation (KCNJ11: C166Y, K170N, L164P, Q52R, R50P - ABCC8: A1263V, Q211K, R1182W, T229N, V86A). Digestive disorders in the days following the introduction of SU were the main reported adverse effects.

Conclusion: SU alone are efficient to allow a good metabolic control in 88% of patients with permanent neonatal diabetes owned to KCNJ11 mutation and in 84% of patient carrying a mutation ABCC8 gene. Nor significant side effects were reported. This study is, to our knowledge, the only review of the literature aimed at identifying the SU of mutant potassium channels in vivo.

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